The Painless Stop Smoking Cure

Quit Smoking Magic

Quit Smoking Magic is the first and Only program of its type that literally can Force You to easily kick the habit in just days even if you have a shoestring budget and absolutely no will power. Benefits: Helps You to successfully quit smoking in as little as just days. Its as easy as taking candy from a Sleeping baby. This system takes just minutes to administer. This system can be done on a shoestring budget. Absolutely no chance of Any negative side effects. Works for almost Everyone 98% success rate thus far. You will never relapse with this program. Theres no Will-power necessary with Quit Smoking Magic. Powerful concept based on Real-life experiences rather than just theories. Quit Smoking Magic Teaches You: How to quit smoking cigarettes super-fast. How to stop your Cravings dead in their tracks. How to Never relapse with this nasty habit. How to avoid spending a ton of Money in your quest for quitting. How to quit smoking Now rather than later. How to Automatically kick this habit even without will-power. How to keep from having withdrawal symptoms and nasty mood swings. How to refrain from having Insomnia after quitting. How to avoid restlessness as well as changes in appetite. Read more...

Quit Smoking Magic Overview


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Author: Mike Avery
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My Quit Smoking Magic Review

Highly Recommended

The author presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this manual are precise.

When compared to other e-books and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

The Neurobiology of Nicotine Dependence

Animal research has demonstrated that nicotine exerts its reinforcing effects via the ventro-striatal pathway by increasing dopamine (DA) release in the nucleus accumbens and the pre-frontal cortex (PFC), in a similar way as other drugs of abuse (Nestler, 2005). Nicotine binds to the neuronal a4 2 nicotinic acetylcholine receptors (nAChRs) located on the dopaminer-gic cell bodies in the ventral tegmental area (VTA) (Mifsud et al, 1989). Stimulation of these nAChRs by nicotine produces a shift from tonic firing of dopaminergic neurons to burst firing, resulting in increases in DA levels in the nucleus accumbens (Grenhoff et al, 1986 Mansvelder et al, 2003 Nisell et al, 1994). The meso-limbic dopaminergic pathway is under the influence of other neurochemical modulators such as GABA-ergic interneurons (Kalivas, 1993) and GABA-ergic innervations from the nucleus accumbens (Walaas andFonnum, 1980), both of which provide inhibitory control over DA neurons. In addition, glutamergic...

Smoking Initiation and Dependence

Several twin studies have demonstrated that there are strong genetic factors that contribute to smoking behavior (Hopfer et al, 2003 Li, 2003). Meta-analyses of twin studies suggest that 50-60 of the variability in smoking initiation is attributable to genetic factors (Li et al, 2003 Sullivan and Kendler, 1999 Vink et al, 2005). There is evidence to suggest that the her-itability estimate for smoking initiation might be greater for males (Hamilton et al, 2006), though the opposite has also been observed (Li et al, 2003). Adoption studies (that control for confounding factors) have demonstrated that adoptees raised in separate environments had a greater likelihood of being a current smoker if their biological siblings were smokers (OR 3.2) or ex-smokers (OR 2.6) (Osler et al, 2001). In addition, genetic factors account for 60-70 of the variability in smoking rate and level of nicotine dependence (Haberstick et al, 2007 True et al, 1999 Vink et al, 2005), with greater heritability among...

Smoking Cessation and Persistence

Results from recent twin studies and a meta-analysis indicate that heritability estimates associated with smoking persistence range from 60 to 70 (Hamilton et al, 2006 Hardie et al, 2006 Sullivan and Kendler, 1999). Genetic factors also contribute significantly toward determining the results of cessation attempts and self-reported level of withdrawal symptoms (Xian et al, 2003), as well as the duration of cessation (Hardie et al, 2006). Adoptee smokers who had quit smoking had a three times greater odds that their biological siblings were ex-smokers as well (0sler et al, 2001).

Genetic Associations with Nicotine Reward

The relative reinforcing value of nicotine can be evaluated using the cigarette choice paradigm. In this procedure, participants are given the opportunity to choose between smoking a regular nicotine cigarette vs. a denicotinized cigarette, but they are blinded as to which cigarette contains nicotine. Female participants with the low-activity (G or Asn40) allele at the OPRM1 gene showed reduced reinforcement from cigarettes in this paradigm since they chose equally between the nicotine and the denicotinized cigarette (Ray et al, 2006). Individuals with the G allele were also less likely to distinguish between either cigarette based on self-report measures of satisfaction and strength (Ray et al, 2006). In a separate trial, haplotypes on the cyclic AMP binding protein 1 (CREB1) interacted with OPRM1 genotype to effect nicotine reward specifically, while the CREB1 genotype had little effect on nicotine reinforcement between naltrexone and placebo for those with the OPRMI G allele, there...

Genetic Associations with Nicotine Sensitivity

Nicotine sensitivity was tested by administering nicotine nasal spray to non-smokers and recording self-reported mood changes. Individuals with the DRD4 7-repeat allele reported higher levels of aversive reactions to nicotine exposure as well as reduced nicotine choice (Perkins et al, 2008a). Men with the TT genotype at DRD2 C957T had greater subjective effects after nasal spray administration (Perkins et al, 2008a). In a separate study, the non-synonymous SNP located on CHRNA5, which has been linked with nicotine dependence, was associated with self-reported pleasurable rush or 'buzz' during the first cigarette of the day (Sherva et al, 2008). Two polymorphisms on CHRNB3 also have been associated with subjective responses to initial tobacco use among adolescents (Zeiger et al, 2008). A functional SNP on CHRNA4 has been associated with nicotine sensitivity with smokers possessing the TC genotype, compared to the CC genotype, reporting increased physiological and cognitive effects...

Treatment of Lung Cancer Associated Anemia 161 Transfusions

Historically, treatment options for patients with lung cancer who develop severe or symptomatic anemia were primarily limited to RBC transfusions. In fact, most physicians still do not treat, unless with RBC transfusion, in case of severe anemia (5). Although RBC transfusion is the most rapid correction, especially useful in patients with severe or life-threatening anemia, several risks are associated with it, including acute transfusion reactions and transmission of infectious agents (71,72). Furthermore, the limited availability and the cost of transfusion products limit their use. Finally, there is the concern of decreased immunosurveillance of tumors by the recipient of allogeneic transfusion. A negative impact on outcome has been described in some but not all surgical series examining this issue in lung cancer (73) and other cancer types (74,75). Another treatment option for the management of anemia is the administration of rHuEPO. The Food and Drug Administration (FDA) approved...

Nonsmall Cell Lung Cancer

Randomized Studies on the Primary Use of White Blood Cell Colony-Stimulating Factors in Chemotherapy for Advanced Nonsmall-Cell Lung Cancer Randomized Studies on the Primary Use of White Blood Cell Colony-Stimulating Factors in Chemotherapy for Advanced Nonsmall-Cell Lung Cancer

Other environmental risk factors that may predispose smokers to COPD

In addition to cigarette smoking a number of environmental factors have been identified which impact on lung function (FEV1) and may therefore predispose to the development of COPD. These are summarized in Table 26.4. The identification of low birth weight (Barker et al., 1991), childhood respiratory tract infections (Burrows et al., 1977b Colley et al., 1973 Kiernan et al., 1976) and childhood passive smoke exposure (Lebowitz et al., 1987 Wang et al., 1994) as factors that may contribute to the pathogenesis of COPD suggests that the disease may begin in childhood. However, these observations are often derived from retrospective studies and the results need to be interpreted with caution (Phelan, 1984). In adults, increased expression of adenovirus protein in smokers with emphysema has provided evidence that latent viral infection may amplify the inflammatory response to cigarette smoke and contribute to the development of emphysema (Retamales etal., 2001). Occupational exposure to...

Lung Cancer Treatment

EGF receptor regulates the growth of many types of cells. EGF receptor overexpression is common in lung cancer. The EGF receptor can be blocked by an Ab such as the human-chimeric MAb cetuximab that binds to its extracellular domain or by small molecules such as gefitinib, a reversible inhibitor of EGF receptor tyrosine kinase (94,99). In two large phase 2 trials of patients previously treated with chemotherapy for nonsmall-cell lung cancer (NSCLC), response rates of up to 19 were reported for gefitinib (100,101).

Small Cell Lung Cancer

Randomized Studies Focusing on the Primary Administration of White Blood Cell Colony-Stimulating Factors in Small-Cell Lung Cancer Randomized Studies Focusing on the Primary Administration of White Blood Cell Colony-Stimulating Factors in Small-Cell Lung Cancer Randomized Studies on the Primary Use ofWhite Blood Cell Colony-Stimulating Factors in Standard-Dose Chemotherapy for Small-Cell Lung Cancer Randomized Studies on the Primary Use ofWhite Blood Cell Colony-Stimulating Factors in Standard-Dose Chemotherapy for Small-Cell Lung Cancer Randomized Studies on the Primary Use ofWhite Blood Cell Colony-Stimulating Factors to Increase Dose Intensity of Chemotherapy for Small-Cell Lung Cancer

Nicotine Dependence

In studies of adult smokers, there is strong evidence linking the CYP2A6 gene with nicotine dependence, with fast metabolizers being at greater risk for developing dependence. There is also substantial evidence linking the CHRNA5-A3-B4 gene cluster to nicotine dependence in several different populations. The dopaminer-gic system is thought to play a key role in the experience of nicotine reward, and this is supported by some genetic evidence for associations of nicotine dependence with the ANKK1 gene. Associations of the DRD4, COMT, and OPRM1 genes with nicotine dependence remain suggestive and additional studies are needed to confirm

Smoking Cessation

The phenotypic marker for CYP2A6 activity, the nicotine metabolite ratio, is differentially associated with treatment response to both NRT and bupropion. These findings suggest that slower metabolizers derive greater nicotine from a standard dose of nicotine patch and have greater success with this treatment, compared to faster metabolizers. Alternatively, bupropion is an effective medication with efficacy for this risk group. Thus, one mechanism is likely to focus on the reduced dose of treatment achieved from nicotine replacement products in the slow vs. fast metabolizers, while bupropion targets a different neurobiological mechanism (dopaminergic system). The CYP2B6 enzyme is responsible for bupropion metabolism, and polymorphisms that are known to decrease CYP2B6 activity have been associated with a more favorable treatment response with bupropion across studies. The COMT val158met polymorphism has been related to success with nicotine replacement therapy in independent studies....

Lung cancer

Cancer of the lung is the leading cause of cancer-related death in males and the incidence is rising in females. Regrettably it is closely related to tobacco smoking and control in the future depends largely on government measures to reduce tobacco consumption. From a practical point of view, lung cancers are categorized as small or non-small cell cancers. Table 18.2. World Health Organization histologic classification of lung cancer.

John M Walker Series Editor

Lung Cancer Volume 2, Diagnostic and Therapeutic Methods and Reviews, edited by Barbara Driscoll, 2003 74. Lung Cancer Volume 1, Molecular Pathology Methods and Reviews, edited by Barbara Driscoll, 2003 73. E. coli Shiga Toxin Methods and Protocols, edited by Dana Philpott and Frank Ebel, 2003 72. Malaria Methods and Protocols, edited by Denise L. Doolan, 2002

The Scope Of Biosurveillance

We also decided against disease surveillance and public health surveillance because these terms, to an epidemiologist, connote surveillance for noninfectious disease, child mortality, injury, cigarette smoking, and dental diseases such as enamel fluorosis (CDC, 2005). To keep what was already a very large topic manageable, we decided against discussing surveillance for these conditions. The principles and techniques that we discuss, nevertheless, apply to surveillance for any disease or condition.

International Variation In Rates

The remarkable international variation in cancer rates, for many of the common cancers, such as breast and prostate, seemed to many to support the traditional view that endogenous hormones could not be the sole or primary cause. The low rates of breast, prostate, and several other cancers in Asian populations and their increase toward Western rates upon migration to the United States or Europe suggested that chemical factors or other environmental agents were the major causes of these cancers. While cigarette smoking was one such obvious chemical carcinogen, which would help to explain the international variation in lung and other smoking-related cancer sites, the most obvious cause of the other cancers seemed to be diet, other lifestyle factors, or unidentified environmental agents. In 1964, an expert committee of the World Health Organization stated that the categories of cancer that are thus influenced, directly or indirectly, by extrinsic factors . . . collectively account for...

The Persistence of Time

An example of interval timing data collected from an adult participant (ALB) diagnosed with attentional-deficit disorder (ADD) using the PI procedure is shown in Figure 1. The top panel illustrates percent maximum response rate for ALB in an unmedicated state (NicPre) plotted as a function of 7-s and 17-s criteria trained using methods reported by Levin et al, 1996, 1998 Rakitin et al., 1998. In this procedure, a blue square presented on a computer monitor is transformed to magenta at the appropriate criterion time during fixed-time training trials. Thereafter, participants are requested to reproduce the temporal criterion for a sequence of test trials for which a distribution of their responses is plotted on a relative time scale immediately following the trial during the inter-trial interval (ITI). This ITI feedback is displayed on the computer monitor and provides the participant with information concerning the relative accuracy and precision of their temporally-controlled...

Nature and Essentially of Cofactors

Cofactors are small, mostly nonpeptide compounds which are required for activity of some enzymes. These include organic compounds, such as NAD+ (nicotine adenine dinucleotide), FAD (flavin adenine dinucleotide), coenzyme B12, triphosphates of adeno-sine (ATP), cytidine (CTP), and uridine (UTP), as well as many others (see Ref. 1 and references cited therein). They also include many inorganic cations and anions as well as metallo derivatives of organic compounds (coenzyme B12, metal-porphyrin cofactors). See Table 2 for some specific examples.

Health benefits of whole foods over isolated components

Volunteers were given relatively high dose supplements of b-carotene for several years, which substantially raised plasma and, presumably, tissue concentrations. These studies showed one of two things, either supplementation with b-carotene was not effective with regard to CVD, cancer or all-cause mortality or, in susceptible individuals like smokers and asbestos workers, the mortality rate from lung cancer was significantly increased. On the other hand, plasma b-carotene concentration (reflecting the consumption of carotenoid-rich foods) before supplementation was inversely and significantly associated with lower cancer rate.

The use of functional foods to meet dietary guidelines

Foods enriched with fibres and vitamins can be an alternative to fruits and vegetables, but only to a certain point. For example, different dietary fibres have different effects on CVD risk water-soluble dietary fibres such as pectin and guar gum appear to have stronger effects than insoluble fibres such as wheat bran.24,25 Thus, a mixture of various dietary fibres such as found naturally in fruits and vegetables appears to be necessary for a protective effect on CVD. Also, adding vitamins to foods to compensate for low fruit and vegetable intakes might not have the expected effects. For example, beta-carotene was widely believed to reduce cancer risk in smokers, because intake of carotene-rich foods was associated with less cancer, as were high levels of carotene in blood. However, it was found that carotene supplements increased risk of lung cancer in smokers.26 27 Large clinical trials of antioxidants have also had disappointing outcomes.28 Moreover, several other bioactive...

Do functional foods reach the populations at risk

Several surveys have shown that a higher socioeconomic status is associated with a healthier diet, that is, a diet closer to the recommendations.10'45 Consumers with a low or middle socioeconomic status would therefore benefit most from functional foods. It has been suggested that functional foods would appeal most to healthy, well-educated and rich consumers, but this does not appear to be true in a Dutch survey among 1183 consumers aged 19-91 years, determinants of functional food use depended on the type of food.46 Stanol-enriched margarines were consumed most by smokers and consumers with a poorer subjective health. A Finnish study, however, showed a higher consumption of such margarines in consumers with higher socioeconomic status.47 Differences in marketing strategies can possibly account for these differences.

Microsatellite instability in cancer progression

Microsatellite instability has been encountered in several forms of human cancer, e.g. in colonic (Aaltonen et al., 1993 Ionov et al., 1993 Thibodeau et al., 1993 Patel et al., 1994), endometrial (Risinger etal, 1993 Burks etal., 1994), gastric (Han etal, 1993 Peltomaki etal., 1993 Seruca et al., 1995 Dossantos et al., 1996), pancreatic (Han et al., 1993), and oesophageal cancers (Meltzer et al., 1994). This abnormality was not found in cancers of the breast, lung or testis (Peltomaki et al, 1993), but recent reports do cite microsatellite instability in these tumours. MI may occur infrequently in sporadic and in familial breast cancer (Jonsson et al., 1995) and at a high frequency in invasive lobular breast carcinoma (Aldaz et al., 1995). Merlo et al. (1994) has stated that it occurs frequently in small cell lung carcinoma. Adachi et al. (1995) found no MI in small cell lung carcinoma, but did find MI in about one-third of non-small cell lung cancers. Instability of microsatellite...

Glycocholate Breath Test

Breath test is a simple, inexpensive, and noninvasive technique to diagnose SBBO. The lactulose breath test is performed after 12 hours fasting previous to the test. Hydrogen breath samples are taken at baseline, and subsequently every 10-30 minutes after the test meal that contains 10-12 g of lactulose. The hydrogen breath samples are analyzed gas chromatographically (81). Baseline samples average 7.1 +5 parts per million (ppm) of H2 and 0-7 ppm for CH4 (82). Values of the baseline sample over 20 ppm H2 are suspect for bacterial overgrowth. Values between 10 and 20 suggest incomplete fasting before the test or ingestion of slowly digested foods the day before the test, the colon being the source of the elevated levels (82). Slowly digested foods like beans, bread, pasta, and fiber must not be consumed the night before the test because these foods produce prolonged hydrogen excretion (82). The patient is not allowed to eat during the complete test. Antibiotics and laxatives must be...

Arthur A Stone and Saul S Shiffman

Asking people about their health, symptoms, attitudes, opinions, and behaviors is ubiquitous in the behavioral, social, and medical sciences (Stone et al, 2000). For many areas of inquiry in these fields, it is impossible to contemplate research programs without self-reports. Self-reports often serve as primary outcome measures, for instance, in assessing pain, fatigue, opinions, or attitudes self-reports are the accepted standard for these constructs and objective alternative measures usually are not available. Even when objective measures are possible in principle, we often rely on self-report data (e.g., smoking behavior, asthma attacks, social interactions), because the costs of objective data collection (via behavioral observations, for example) are prohibitive.

The Quantitative Burden Based On Cancer Statistics

Treatment success and survival rates, similar to incidence, are heterogeneous when calculated for specific cancer site. For selected cancers, the annual age-adjusted cancer incidence rate for men and women are shown in Figure 3.14 As noted, for the two most common cancers, prostate cancer in men and breast cancer in women, the incidence continues to substantially increase. The age-adjusted death rates for various cancers are shown in Figures 4 and 5 for women and men respectively.14 As noted, the death rate for the common cancers, breast, colorectal, stomach, and prostate cancer are in decline. Remarkably, the death rate for lung cancer in men is also in decline leading to the overall diminished cancer mortality unfortunately, a similar decline has not yet been observed for women.

Conclusion and Outlook

In the last 50 years, epidemiologic research has identified a large number of risk factors and preventive factors of multiple chronic diseases, yet the transfer of these findings into applied disease prevention has often remained unsatisfactory. For example, half a century after the deleterious health effects of smoking have been disclosed by carefully conducted epidemiologic studies, the global number of smokers and prevalence of smoking keep rising. A similar development appears to be seen for physical inactivity, which is likewise related to a large number of severe chronic diseases. Therefore, further development of epidemiology in aging research has to go along with research on how to more effectively translate epidemiologic study results into the practice of prevention. Preventive efforts again have to keep the entire life span in mind.

Dietary strategies to prevent the development of heart disease

Most investigators agree that atherosclerosis is a chronic low-grade inflammation disease.29 Pro-inflammatory factors (free radicals produced by cigarette smoking, hyperhomocysteinaemia, diabetes, peroxidised lipids, hypertension, elevated and modified blood lipids) contribute to injure the vascular endothelium, which results in alterations of its antiatherosclerotic and antithrombotic properties. This is thought to be a major step in the initiation and formation of arterial fibrostenotic lesions.29 From a clinical point of view, however, an essential distinction should be made between unstable, lipid-rich and leucocyte-rich lesions and stable, acellular fibrotic lesions poor in lipids, as the propensity of these two types of lesion to rupture into the lumen of the artery, whatever the degree of stenosis and lumen obstruction, is totally different.

P53 cancer progression and prognosis

Whether mutations of p53 reflect progression of the disease cannot yet be established. In order that this may be assessed it is important to determine whether these are temporal changes and whether they are progressive and cumulative. It is also necessary to examine whether there is also a topographical change in the pattern of expression of the p53 protein. In oesophageal and lung cancers,p53 abnormalities arise early (Casson etal., 1991 Bennett etal., 1992 Sozzi et al., 1992). A low frequency of point mutation may be found in one in 10 squamous cells and in one in 14 adenocarcinomas in oesophagus mutations have also been found in four out of seven Barrett's epithelium adjacent to the adenocarcinomas, possibly related to pre-malignant changes Somewhat intriguing, but nonetheless relevant in this context, is the observation in some studies that patients who have gliomas with mutated p53 have survived significantly longer than patients whose tumours contained no mutations (van Meyel,...

Project Title Cardiac Mr Of Subclin Cvd Impact Of Age

Summary (Verbatim from the Applicant's Abstract) Coronary heart disease and stroke are leading causes of mortality for men and women in the United States. Our current understanding of the pathogenesis of and the risk factors for cardiovascular disease (CVD) is derived largely from prospective studies of clinically overt disease. Unfortunately, clinical risk factors for CVD defined by these methods fail to predict a large proportion of CVD events, and some subjects at high clinical risk fail to develop overt disease. Subclinical disease precedes clinical events by years decades but is difficult to quantify. For example, left ventricular hypertrophy (LVH) and aortic atherosclerosis are strong predictors of CVD events, but are difficult to accurately non-invasively quantify, especially among the elderly and overweight subjects (both growing populations in the U.S.). MRI perrnits accurate assessment of cardiac anatomy function and subclinical aortic atherosclerosis. The underlying...

Implementing Interventions

Causal features and consequences will be critical for specific interventions. For example, asthmatics may be concerned about causal features and consequences of corticosteroid use because the term steroids evokes consequences seen in athletes' drug use, and inhaling is perceived as similar to using other substances, eliciting fears of addiction. Similarly, conceptualizing cancer as caused by either gene mutations (e.g., BRCA1) or behaviors (e.g., smoking) may result in very different post-treatment monitoring and management behaviors. As behaviors can be altered, a belief in behavioral causes could encourage patients to quit smoking, engage in regular exercise, and or follow a healthy diet. On the other hand, genes are associated with immutability, which could lead to inaction.

Introduction oxidative stress and cardiovascular disease

The literature reviewed below strongly suggests that oxidative stress plays a key role in the etiology of cardiovascular disease. Oxidative stress is a physiological condition in which pro-oxidant factors outweigh antioxidant defences. Accordingly, the role of oxidative stress in promoting cardiovascular disease and the roles of fat-soluble antioxidant nutrients in potentially protecting from this disease process will be discussed in some detail. Oxidative stress is likely to occur during inflammatory processes, during exercise and from cigarette smoking. The evidence presented below also suggests that vitamin D plays an important and significant role in preventing cardiovascular disease but it is very unlikely that this effect is related to its potential role as an antioxidant.

Examples of use of stereotaxic injection for psychiatric research

Stereotaxic injection is also beginning to be used in research on drug, alcohol, and nicotine abuse. Mice with knockout of b2-subunit of the nicotinic acetylcholine receptor have been reported to fail to display nicotine reinforcement behaviors. The reintroduction of the b2-subunit into the VTA (ventral tegmental area) by using a lentiviral vector to reinstigate sensitivity to nicotine reward, however, demonstrates the sufficient role of the VTA in nicotine reinforcement (Maskos et al., 2005).

Project Title Community Surveillance Of Cardiovascular Diseaserisk F

Summary Data from the most recent survey (1995-97) of the Minnesota Heart Survey (MHS) indicate that previously favorable trends in cardiovascular risk factor levels are attenuating. While cigarette smoking and self-reported dietary fat intake continued to decline, mean body weight rose substantially and rapidly, physical activity decreased, and the previous decline in serum total cholesterol was no longer apparent. These trends may or may not continue in the future. As part of the Minnesota Heart Survey, we propose to conduct another population survey of 4,000 adults, ages 25-84 years in 2000-02, to detect current trends in cardiovascular disease risk factors, including serum lipids, blood pressure, cigarette smoking prevalence, dietary fat intake, obesity, diabetes, physical inactivity, fibrinogen, and serum vitamin E. The proposed survey will build upon four previous, independent cross-sectional surveys conducted in 1980-82, 1985-87, 1990-92, and 1995-97, which collectively...

Social History And Habits

Smoking history can also make pain management more difficult at times not only because of the patient's compromised pulmonary function, but also because of nicotine withdrawal, which can make the patient restless and less able to cope with pain (81-86). Other important habits (e.g., bowel habits and laxative use) should also be evaluated before ini

Health Maintenance And Disease Prevention

Smoking and consumption of alcoholic beverages. But despite the efforts of schools, the government, and other organizational spokespersons to convince people to get a good night's rest, eat breakfast, stop smoking, drink alcohol in moderation (if at all), and exercise, a substantial portion of the population continues to resist those recommendations (see Figure 3-6). The consequence of such an unhealthy lifestyle is pain, disease, and a shortening of the life span.

Retinoblastoma susceptibility gene rb abnormalities in cancer

The rb gene is expressed in all normal tissues and cell lines (Lee et al., 1987b). It is expressed in a mutated form or absent in retinoblastomas (Lee et al., 1987b, 1990 Horowitz et al., 1990). Abnormalities of this gene have been described in several other human tumours, e.g. small cell lung cancer (SCLC) (Harbour et al., 1988 Hensel et al., 1990 Mori et al., 1990). Harbour et al. (1988) found that 13 of primary SCLC and 18 of SCLC-derived cell lines showed structural abnormalities of rb and 60 of SCLC-derived cell lines showed a loss of the gene. Loss of gene expression has been reported in 30 of primary non-SCLCs (Xu et al., 1991) and it appears also from this study that altered rb expression may be related to tumour stage. Inactivation of rb was reported in two bladder cancer cell lines and lack of expression without gross gene deletion in another cell line (Ishikawa et al., 1991). Of considerable interest is the suggestion of rb inactivation with tumour progression. For these...

Cholinergic Mechanisms

Application of nicotine to intrathoracic autonomic neurons can alter their activity (68) and induce concomitant changes in regional cardiac function, whether the neurons are located in extracardiac or intrinsic cardiac ganglia (68,140). Nicotinic activation of intrinsic cardiac neurons evokes a biphasic cardiac response, with initial suppression in regional cardiac function being followed by augmentation (Fig. 6). Nicotinic activation of atrial intrinsic cardiac neurons modifies primarily, but not exclusively, atrial function, whereas nicotinic activation of ventricular intrinsic cardiac neurons modifies primarily, FIGURE 6 Chronotropic and atrial inotropic effects elicited by injecting nicotine into a locus of the dorsal right atrial ganglionated plexus (RAGP) before (control) and following sequential selective muscarinic (atropine) and then ft-adrenergic (propranolol + atropine) blockade. The dorsal right atrial ganglionated plexus is primarily associated with the control of right...


The following tests should be performed on all patients with AIDS a lumbar spine X-ray in the standard anteroposterior and lateral views, bone density measurement (DEXA scan) of the lumbar spine and hip and laboratory blood tests, including calcium, phosphate and alkaline phosphatase. Osteopenia should be treated with 1000 I.E. vitamin D daily and a calcium-rich diet or calcium tablets with a dose of 1200 mg day. Patients should be advised to exercise and give up alcohol and nicotine. In cases with osteoporosis, bisphosphonates (e.g. alendronat 70 mg once a week) should be added. The tablets should be taken on an empty stomach 30 min before breakfast, and an upright position should be maintained for at least 30 min. No calcium should be taken on this day. Antiretroviral therapy should not be taken together with calcium. Because testosterone suppresses osteoclasts, hypogonadism should be treated. Alcohol and smoking should be avoided regular exercise is an essential part of the therapy.

Adenoassociated Virus For Immunotherapy

The potential of AAV vectors for cancer immunotherapy is evident from recent studies using cytokine gene transfer and in vivo immunization approaches (108-110). Active immunization with tumor cells transduced with rAAV encoding cytokines either by a plasmid based-delivery system or by a recombinant virus-mediated infection has resulted in regression of tumor growth upon further challenge. In a separate study, high-level IFN-y and elevated major histocompatibility complex (MHC) class I expression was observed following transfer of D122 gene-modified murine lung cancer cells that significantly delayed tumor development (111). Similar findings of antitumor immunity following transfer of cytokine-encoding AAV DNA in a rat prostatic tumor model (112) were reported. Enhancements in antitumor T-cell response was observed in vitro by AAV-mediated transduction of B7.1 and B7.2 genes in a human multiple myeloma cell line (113). In a vaccination scheme, Liu et al. have recently shown that...

Drug Dependency Assessment

Similar withdrawal symptoms can also occur with sedatives, anticonvulsants such as clonazepam and carbamazepine, and muscle relaxants such as carisoprodol (11-13,127). Frequent nicotine and caffeine use is also an important consideration in pain management. Nicotine abstinence symptoms can cause restlessness, palpitation, and irritability, and caffeine abstinence can precipitate headaches.

Differentiating Between Classes of Norms

Much of the early debate concerning the utility of norms focused on the lack of a commonly agreed upon definition of the construct. However, Cialdini et al's (1990) formulation classifying norms into two distinct categories, descriptive and injunctive, has set the standard for subsequent research. Additional characterizations of norms have been identified and studied (e.g., personal norms Schwartz, 1977) however, the focus at present will be on descriptive and injunctive norms. Descriptive and injunc-tive norms distinguish, respectively, between perceptions of what is and what ought to be. While descriptive norms refer to perceptions of how others typically behave in a given situation, injunctive norms capture what is commonly approved or disapproved (Cialdini et al, 1990). For example, perceiving that the majority of individuals in one's immediate environment are smoking cigarettes, or that most of one's family, friends, coworkers, etc., are smokers, would be Questions have been...

Relationships of Norms to Health Behaviors

Correlational research supports roles for descriptive and injunctive norms in the longitudinal prediction of both health-protective and health-risk behaviors. Etcheverry and Agnew (2008) documented relationships of both friends' use and approval of cigarettes with the number of cigarettes smoked over time. Similarly, in their meta-analysis, Sheeran et al (1999) observed relationships of both norms to condom use. However, descriptive norms exhibited a significantly larger relationship with the outcome than did injunctive norms. Research has also found only descriptive norms to be predictive of alcohol consumption and needle sharing among injection drug users (Carey et al, 2006 Davey-Rothwell et al, 2009). Additional research supports only a role for injunctive norms in the prediction of alcohol use (Larimer et al, 2004). Accordingly, it is unclear whether either category of norms consistently weighs more heavily than the other in decisions to perform health-protective or health-risk...

Joel N Hirschhorn Celeste Leigh Pearce David Altshuler

Some circumstances, such as the role of smoking in lung cancer,4 a single environmental exposure can make a major contribution to disease risk. In other cases, such as early-onset breast cancer, exposure to a mutation in a single gene can be both necessary and sufficient to cause dis-ease.5,6 In the population, however, most cancers are attributable neither to a single identifiable environmental factor nor to mutation of a single gene. Rather, cancer typically results from a combination of factors inborn and somatically acquired mutations in gene sequence, one or more environmental factors, and certainly an element of bad luck. Such disorders are referred to as complex traits. This complexity has thus far befuddled researchers where the web of causality is broad, any single strand plays only a minor role and eludes most efforts at discovery.

Consequences of Misperceptions for Behaviors

Similar findings have been obtained in relation to other problematic behaviors. For example, perceptions of the prevalence of peer use of cigarettes and marijuana predict personal cigarette and marijuana use (Graham et al, 1991 Juvonen et al, 2007). The body image and disordered eating literatures have documented disturbing relationships of perceived norms for weight and body size with unhealthy behaviors among young women. Sanderson and colleagues (2002) found that women who had greater discrepancies between their own body mass index and the perceived average body mass index of their peers were at increased risk for both experiencing an extreme desire to be thin and engaging in behaviors that are symptomatic of bulimia, such as binging and purging. Similarly, Bergstrom et al (2004) documented greater unhealthy weight loss behaviors, including vomiting, fasting, and use of laxatives and diuretics, among women who overestimated men's endorsement of overly thin women as attractive.

Acetylcholine as a Neurotransmitter

The stimulatory effect of ACh on skeletal muscle cells is produced by the binding of ACh to nico-tinic ACh receptors, so named because they can also be activated by nicotine. Effects of ACh on other cells occur when ACh binds to muscarinic ACh receptors these effects can also be produced by muscarine (a drug derived from certain poisonous mushrooms).

Introduction It Is About People

It may seem a long stretch from Helen's success in running a local pub to a text book on public health, but she does have a crucial common agenda with those working in infant immunization, smoking cessation, and obesity prevention she too is dealing in voluntary behavior change. She wants - needs - people to visit her pub, buy her beer, tell their friends and family what a good pub it is, visit her pub again, organize their wedding receptions with her And she knows they have a choice she cannot compel them to do these things, so she has to seduce them. This means she has to understand their needs absolutely and cater to them at every opportunity. She has to avoid the trap of taking refuge in the technicalities of her work, focusing purely on the science of good beer or minutiae of stock management. These things matter, but only in so far as they help her meet her customers' needs. As with the King's Head, so with smoking cessation. Case Study A shows how a service in the North East of...

Clear Behavioral Objectives

Social marketing has to begin with a definitive statement of behavioral objectives exactly what we want who to do (or to stop doing). Without this clarity it is impossible to either decide about methods or monitor progress. Behavioral objectives are often incremental, building gradually to the final, and often longer term goal. For example, if we want to help people stop smoking, intermediate objectives might include attending quit services setting quit dates stopping smoking or staying quit for a target time with proof (as with carbon monoxide monitors).

Oral diseases and cariogenicity

Oral refers to the mouth, and includes the teeth and gums (gingival) and their supporting tissues, the hard and soft palate, the mucosal lining of the mouth and throat, the lips, salivary glands, chewing muscles, and upper and lower jaw bones. Digestion begins in the oral cavity, and there are numerous supporting structures for the mouth including the nervous, vascular, and immune systems. Humans contract oral diseases for a number of reasons including genetics, poor hygiene, poor nutrition, alcohol and tobacco use, drug abuse (Shaner et al., 2006), and complications from other diseases such as diabetes (Sandberg et al., 2000, Twetman et al., 2002), cancer (Woo et al., 1993), obesity (Ritchie and Kinane, 2003), and osteoporosis (Norlen et al., 1993). Oral infections themselves may play a role in progressing pathogenesis of many systemic diseases in healthy individuals, ill patients, and those immunocompromised (Ridker et al., 1998). The theory is that oral infections, specifically...

Historical Significance

In January 2003 a disgruntled grocery worker tainted approximately 200 pounds of ground beef sold at a supermarket in Michigan. At least 92 patients had clinical presentations consistent with nicotine-containing pesticide intoxication. Epidemiology and lab studies confirmed that the food product had been contaminated at the level of the local grocery store, and not at a higher level in the food supply chain. Unintentional contamination with pesticides also has been reported.

Conclusions And Future Directions

PET provides the opportunity to image multiple dynamic biological processes in situ in brain tumors. Energy metabolism and amino acid transport and incorporation are important components of the pathophysiology of gliomas about which molecular imaging is providing regional biological information that is useful in clinical practice. Imaging hypoxia is straightforward and proliferation imaging with FLT shows significant promise. Neither has been exploited thoroughly enough to allow judgment of their potential benefit to the practice of neuro-oncology. Whereas cell division is the most distinguishing function ofgrowth in tumors, probing membrane biosynthesis with PET and 1- C-11 acetate or a choline tracer may yield information as helpful as protein or DNA synthesis. Because astrocytic gliomas frequently carry epidermal growth factor receptor mutations at a frequency that is related to grade, a PET tracer specific for this mutated receptor could be useful for grading and prognosis (127)....

Overexpression of Tumor Suppressor Genes and Apoptosis Inducing Genes

The fact that overexpression of tumor suppressor genes and apoptosis-inducing genes can induce cell-cycle arrest or apoptosis has led to numerous experimental and clinical investigations into their use as anticancer therapeutics (37,40). Transfer of various tumor suppressor genes directly into cancer cells has been demonstrated to suppress tumor growth by inducing apoptosis and cell-cycle arrest while also exerting lethal bystander effects. Adenovirus-mediated p53 gene therapy has produced promising results in lung cancer and head and neck cancer, among cancers. Combination of tumor suppressor gene therapy with conventional anticancer therapy has been shown to yield synergistic therapeutic benefits. In clinical trials, tumor suppressor genes, especially the p53 gene, have been well tolerated and produced favorable clinical responses, including pathologically complete responses, in subsets of patients with advanced disease or cancers resistant to conventional therapy (37).

Risk factors for coronary heart disease CHD the role of oxidative stress

Different stage in a chronic inflammatory process in the artery. The lesions of atherosclerosis represent a series of highly specific cellular and molecular responses that can be described as an inflammatory disease. Possible causes of endothelial dysfunction leading to atherosclerosis include hypercholesterol-aemia, hypertension, diabetes mellitus, cigarette smoking, elevated plasma homocysteine concentrations, infectious microrganisms and ageing. Framingham's studies have shown how each factor and combination of these factors are associated with atherosclerotic diseases.9 All these factors can be associated with oxidative stress.10-15 The beneficial effect of alpha-tocopherol and ascorbic acid is mediated by their antioxidant actions in preventing atherosclerosis. On the other hand, the effect of alpha-tocopherol could also be mediated by its antiplatelet and anti-coagulant actions, which would prevent the thrombotic consequences of atherosclerosis.16'17 Cigarette smoking,...

Environment as determinant of i genotype and ii disease

Second, the environment presents many exposures that directly alter the probability of occurrence of various diseases. Ionizing radiation contributes to the risks of breast cancer and leukemia. Asbestos causes asbestosis and mesothelioma. Environmental tobacco smoke increases the risks of lung cancer and coronary heart disease. Heavy metals induce various forms of organ dysfunction, for example, environmental lead exposure in early childhood impairs neurocogni-tive development. Patterns of exposure to various antigens in early childhood influence the maturation path of the young immune system, and also

Major Mendelian genes versus minor polygenes as predisposers

Most genetic influences on disease risks, however, occur in polygenic situations where any single contributory gene may shift the probability by no more than a few percentage points. Further, it is likely that it is the interacting set of alleles that is most relevant in determining the level of innate susceptibility of an individual to developing a disorder or disease in response to a particular environmental exposure. In recent years it has become apparent that there are multiple genetic loci which contribute to the occurrence of hypertension, a tendency to rapid weight gain, coronary heart disease, colon cancer, lung cancer and so on. This is hardly surprising. After all, the complex metabolism and physiology of the mammalian organism is, fundamentally, under genetic control, in that all proteins and other active molecules are genetically coded for, and the resultant slight interindividual variations in the molecular structure of proteins affect their biological activity.

Prevention strategies whole populations highrisk groups or selected individuals

That second issue goes further than that. As Rose eloquently pointed out, those factors that best explain the occurrence of cases within a population may not best account for the rate of the disease within the population at large. For example, if the population, overall, consumes a high-fat diet, then whether or not an individual smokes cigarettes may best explain whether he she develops coronary heart disease. Meanwhile, the population-wide dietary behavior may be the main source of the elevated rate of coronary heart disease within that population. Consider another example, admittedly extreme, but it helps to make the point. If within a population everyone smoked 20 cigarettes per day, then the prime determinant of individual risk of lung cancer might well be one or more genetic polymorphisms which determine the fate of inhaled carcinogens. Yet it is the smoking that accounts for the overall high rate of lung cancer in that hapless population.

Dietary antioxidants and the prevention of CHD evidence from clinical trials

While most epidemiological studies have demonstrated that dietary intake of vitamin E is inversely related to coronary heart complications, supplementation studies gave conflicting results. Clinical trials with antioxidants have been done in patients with or without previous history of cardiovascular disease (Table 5.2). Surrogate endpoints, such as analysis of atherosclerosis progression, or 'hard' endpoints, such as vascular death and MI, have been used to evaluate the clinical benefits of antioxidant vitamins. The Alpha-Tocopherol-Beta-Carotene-Cancer (ATBC)52 prevention study was a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta-carotene or both reduced the incidence of lung cancer and other cancers. A total of 29 133 male smokers, 50-69 years of age, were randomly assigned to one of four regimens alpha-tocopherol (50 mg per day) alone, beta-carotene (20 mg per day) alone, both...

Impact of Abnormal Results

Abnormal screening results may also have desirable effects, including improvements in health behaviors and increased likelihood of attendance at future screening. However, although there is some evidence that a false positive mammography result increases the likelihood of future screening attendance in the USA, other findings are conflicting and may vary between countries (Brewer et al, 2007). As mentioned earlier, one study found that people who had polyps discovered at sigmoidoscopy screening were more likely to stop smoking and less likely to gain weight than people who were given the all-clear (Hoff et al, 2001).

Creating the Evidence Base

Impact generates over 250,000 articles written in the past decade alone. These studies have varied dramatically and have ranged from disease-specific interventions, for example, effective behavioral interventions for children and adolescents with type 1 diabetes (Nansel et al, 2009) to methodological questions, for example, Internal and external validity of cluster randomized trials (Eldridge et al, 2008). With a few exceptions (e.g., smoking behavior, compliance with medical regimens, certain types of health care use), we have not seen concerted lines of inquiry regarding behavioral antecedents of health and health care. Rather, there have been a plethora of studies regarding various health problems, behaviors, and contexts for behavior. Community education for Environmental Tobacco Smoke reduction Mass media education to reduce tobacco use Diabetes self-management

Translation of Evidence to Practice

Many argue that the impact of research on the public's health has been hampered less by what we do not know and more by failing to more broadly apply what we do know. Examples of the gap between what is known and population-wide behaviors are plentiful in public health (e.g., tobacco use, patterns of physical activity, and spread of infections) (Ginexi and Hilton, 2006 Glasgow et al, 2004). A major barrier in the translation of evidence to practice is the failure to link the work of academic researchers to the needs of practitioners and the ultimate beneficiaries individuals and families. The translation process is fraught with problems such as how and when evidence becomes sufficient to recommend a change in practice, how valid findings can be effectively communicated beyond the A number of observers (for example, Glasgow et al, 2004) have opined that most practice change requires modification of systems and policies to be truly integrated and maintained in the work of practitioners...

Conclusion and future trends reconciling the evidence

Clinical characteristics of patients with low antioxidant status have not been defined and should be studied in the near future. So far, clinical trials with antioxidants included patients without evaluating either oxidative stress or antioxidant status and such indiscriminate enrolment could perhaps account for the negative results of antioxidant trials recently emphasized by meta-analysis.68 A recent report by Meagher et al.69 is highly relevant to this discussion. They fed normal subjects doses of vitamin E ranging from 200 to 2000 mg day for 8 weeks. The highest dose increased plasma vitamin E levels 5-fold, but urinary excretion of isoprostanes and 4-hydroxynonenal (breakdown products of fatty acid auto-oxidation) was unaffected. The results suggest that in normally nourished subjects, additional vitamin E will not necessarily confer any additional antioxidant protection. Earlier studies in cigarette smokers, in contrast, did show a vitamin E effect on plasma isoprostane levels,...

Public Health as Social Movement

Movements have come closest to embodying the precepts of change discussed above. Bringing about widespread change takes time and requires multiple strategies, many, if not most, of which are behavioral in nature (Green and Kreuter, 2004). The most compelling example of public health as a social movement is the movement for tobacco control the gradual reduction in cigarette smoking among Americans that over time led to dramatic decreases in heart disease and cancer, two of the country's most pernicious public health problems. Figure 27.5 illustrates the critical events that have been associated with reductions in adult per capita cigarette smoking in America over the last 100 years. The increase in tobacco consumption and the attendant increases in heart disease and cancer began their rise at the turn of the last century. By the 1960s, cigarette consumption reached its highest level and strong evidence of the relationship between this habit and disease appeared in the public health...

The Need for Robust Tools and Methods

Several large-scale intervention trials occurring over the past three decades are conceptually close to social movements. These have related to cardiovascular disease risk (e.g., the North Karelia Project, the Stanford Five-City Project) (Fortmann and Varady, 2000), smoking behavior (e.g., COMMIT study, Project ASSIST) (Stillman et al, 1999), and cancer risk (5-A-Day Program) (Campbell et al, 1999). Such projects have targeted whole communities, used multiple strategies to modify individual behaviors and concurrently change the social environment in which behaviors are shaped (Elder et al, 1993 Goodman et al, 1996 Merzel and D'Afflitti, 2003). However, available evaluations of multi-strategy, community-wide, large-scale interventions have shown limited effect on population health risks (Merzel and D'Afflitti, 2003). As noted, person-environment response and accommodation to health-related experiences is difficult to measure and analyze. Indeed, outside of bona fide ineffectiveness or...

Neurotoxicantinduced Models Of Parkinsons Disease 6Hydroxydopamine

The 6-OHDA-lesioned rat model has proven to be a valuable tool in evaluating the pharmacological action of new drugs on the dopaminergic system, the mechanisms of motor complications, the neuroplasticity of the basal ganglia in response to nigrostriatal injury, and the safety and efficacy of neuronal transplantation in PD. Extensive pharmacological studies have utilized the 6-OHDA-lesioned rat to investigate the role of various dopamine receptor (D1 through D5) agonists and antagonists, and other neurotransmitter systems (including glutamate, adenosine, nicotine, and opiods) on modulating dopamine neurotransmission. These studies elucidate

Recognition And Treatment Of Pseudohit

HIT is a relatively common complication of heparin therapy. It may be even more common in patients who have baseline platelet activation and PF4 release, as occurs in adenocarcinoma-associated DIC or DKA. Therefore, a patient with early thrombocytopenia attributable to a pseudo-HIT disorder may subsequently develop clinically significant HIT antibodies (Greinacher, 1995) (Fig. 5). Another example is that of a patient with lung cancer and DVT who developed a platelet count rise during intravenous heparin therapy, followed by recurrent thrombocytopenia and, ultimately, venous limb gangrene during anticoagulation with warfarin and ancrod (Fig. 7). In this situation, one might have expected platelet count recovery during a second course of heparin. However, an intravenous heparin challenge resulted in worsening of thrombocytopenia, and the patient had a strong positive assay for HIT antibodies, indicating the concurrence of cancer-associated DIC and HIT.

Gastrooesophageal reflux disease

The majority of reflux responds to lifestyle adjustments and medical treatment. Losing weight, stopping smoking, avoiding spicy foods and alcohol help some people, but most require some form of acid reduction therapy with either H2 antagonists, or PPIs. Surgical intervention is only considered in cases that do not respond to medical therapy, and sometimes when patients request surgery as an alternative to life-long medication. Some patients have only a partial response to high doses of PPIs, and others have relief of the acid-related problems, but still have a large volume of gastric fluid regurgitating into their oro-pharynx.

Investigations of specific cancers Bowel cancer

Epidemiological studies have indicated that meat intake is a risk factor for colorectal cancer. These studies have been varied in design (cohort and case-control), size, population studied, methodology for assessing meat consumption and in their conclusions (reviewed by Potter et al., 1993). Some studies have suggested that red meat is particularly associated with risk of this cancer while others find no effect. Some studies have found protective effects of poultry and fish consumption while the findings of others have not confirmed this. A recent European study, which represents probably the most thorough investigation of this issue to date, found both an increased risk from red and processed meat and a protective effect of fish (Norat et al., 2005). Similar comments of inconsistency can be made about the association between cigarette smoking and colon cancer risk. As qualitatively, if not quantitatively, exposure to tobacco is more readily measured than quantity Slattery et al....

Colorectal Cancer Background and aetiology

Each year colorectal cancer affects 32 000 people in the UK and is responsible for around 22 000 deaths. In males it is second only to lung cancer and in females it falls third behind lung and breast cancer. In the developed world, life-time risk of colorectal cancer is around 1 25 and this is increased by genetic predisposition and certain conditions such as chronic colitis. Colorectal cancer is mainly a disease of the elderly with a marked rise in incidence after age 70 years, however, 10 of individuals are under age 55 years at diagnosis.

Determinants of Gene Expression

In the last few years there has been mounting interest in epigenetics in the biomedical community (Feinberg, 2008). Much of this interest grows out of discoveries suggesting that epige-netic processes serve as pathways through which various chemical, biological, and social exposures can bring about long-term changes in the activity of genes and thereby contribute to the pathogenesis of disease. For example, studies in animal models have shown that some in utero or early-life exposures, like cigarette smoking, vitamin B12, and folic acid, result in epigenetic alterations to genes that regulate metabolism and other key biological processes. Over the long

Gene Replacement Therapy

The p53 gene (also known as TP53) encodes a 593-amino acid phosphoprotein that plays critical roles in several cell processes including cell-cycle regulation and control of apoptosis (16-18). p53 gene mutations are frequent in tumor cells and have been associated with cancer progression and the development of resistance to both chemotherapy and radiation therapy (19-21). The development of gene transfer techniques has facilitated transduction of tumor cells with wild-type p53 (wt-p53). Preclinical studies both in vitro and in vivo have shown that restoration of wt-p53 function can induce apoptosis in cancer cells. Intratumoral injection in animal models of retroviral or adenoviral wt-p53 constructs results in tumor regression for a variety of different tumor histologies, including non-small-cell lung cancer (NSCLC), leukemia, glioblastoma, and breast, liver, ovarian, colon, and kidney cancers (22-28). Several preclinical studies have indicated that gene therapy with Ad-p53 has useful...

Examples of Gene Environment Interaction

Many examples of gene-environment interactions involving health-related behaviors may be cited. For instance, high density lipopro-tein cholesterol (HDL) concentrations have been shown to vary by interaction of dietary fat intake and genetic variation in hepatic lipase, a key enzyme in HDL metabolism (0rdovas et al, 2002 Tai et al, 2003). In addition, the degree of cholesterol lowering achieved by consumption of a polyunsaturated, compared to saturated, fat diet may be predicted by polymorphic variation in genes encoding the cholesterol ester transfer protein (CETP) and lipopro-tein lipase (LPL) (Wallace et al, 2000). An asparagine aspartic acid substitution in LPL has also been shown to magnify effects of cigarette smoking on risk of incident ischemic heart disease (Talmud et al, 2000). Likewise, the e4 allele of the apolipoprotein E gene (APOE) increases smoking-related risk for coronary disease events in prospective investigations (Humphries et al, 2001, 2003). A third health...

Materials and Methods

Taiwanese HCC patients (308) and healthy controls (304) were recruited from Taipei Municipal Jen-Ai Hospital and Kaohsiung Yuan's General Hospital. Informed consent and peripheral blood (PBL) was obtained from all participants. A questionnaire was designed to collect relevant information regarding HCC risk factors, i.e., age at diagnosis, family history of HCC, hepatitis B virus (HBsAg) or C virus infection (anti-HCV antibody), diabetes mellitus, as well as a-fetoprotein, AST and ALT, and cigarette smoking. The protocols were approved by the Institutional Reviewed Boards, Taipei Veterans General Hospital.

Risk Factors for Chemotherapy Induced Febrile Neutropenia

An important and provocative finding in these investigations is the high proportion of overall risk of FN that is present at the beginning of treatment, which is when standard-dose chemotherapy is first given to a previously untreated patient. For years, the treatment paradigm has emphasized the progressive toxicity associated with sequential chemotherapy dosing. Direct and predictable cumulative toxicity for erythroid cells and platelets may occur, but current data suggest that myeloid cells (i.e., neutrophils and monocytes) may show inherently different responses. Careful observation of blood cell counts in patients with small-cell lung cancer (SCLC) treated with up to six cycles of cyclophosphamide, doxorubicin, and etoposide illustrated that neutrophil counts were not progressively lower with each cycle (10). These results suggest that the hematopoietic tissues of the bone marrow adapt to the sequential insults of chemotherapy, just as the bone marrow adapts to produce more...

The Magnitude of the Problem

Nicotine dependence is among the most significant worldwide public health problems with approximately 1 billion current smokers worldwide (WHO, 2008). In the United States, the decline in smoking rates witnessed over the past several decades has stalled and, currently, 20.8 of American adults are current smokers (CDC, 2004, 2006) even worse, the rates of tobacco use in developing nations are rising rapidly (WHO, 2008). It is predicted that tobacco-related mortality will affect as many as 500 million people across the world (Levine and Kendler, 2004 WHO, 2008). Cigarette smoking causes 80-90 of all lung cancer deaths and increases the risk of other cancers, as well as cardiovascular disease, lung disease, and infectious diseases (CDC, 2004). The economic burden of tobacco-related morbidity and mortality worldwide is estimated to be several hundred billion dollars every year (Guindon, 2006). The current available treatment options for nicotine dependence are nicotine replacement therapy...

Antisense Oligonucleotides

Antisense oligonucleotides (ASONs) are a new class of molecularly targeted agents that are transitioning from the laboratory into the clinic. Clinically, these drugs are well-tolerated with favorable toxicity profiles, and laboratory studies have demonstrated that they can be feasibly combined with radiotherapy. ASONs directed against a number of important cellular targets, including the mRNA of c-myb, MDM2, bcl-2, protein kinase C-a, PKA-I, H-ras, c-raf, R1- and R2-subunit of ribonucleotide reductase, and transforming growth factor 2 (105-108) have been investigated in clinical trials. Laboratory studies investigating the potential value of ASONs as radiosensitizers have also been conducted. Survivin is a recently discovered member of the IAP family that plays a dual role in suppressing apoptosis and regulating cell division and interest has been generated on the use of ASONs to target survivin for downregulation (109). A variety of human tumor types including lung, breast, colon,...

Pharmacokinetic Candidate Genes

The primary enzyme responsible for breakdown of nicotine is cytochrome P450 2A6 (CYP2A6), which has several well-characterized variants that decrease enzymatic activity either partially or completely (http CYPalleles cyp2a6.html). Studies have compared individuals with variants associated with slower nicotine metabolism (one or two copies of the null alleles (CYP2A6*2 or CYP2A6*4), or with two copies of the reduced activity alleles (CYP2A6*9 or CYP2A6* 12)), intermediate nicotine metabolism (carriers of a single CYP2A6*9 or CYP2A6* 12 allele), and normal nicotine metabolism (those with CYP2A6*1 alle-les) (Benowitz et al, 2006). A few longitudinal studies of smoking adoption have examined associations with CYP2A6 alleles. In a cross-sectional study, adolescents carrying the slow or reduced activity alleles of CYP2A6 had an increased odds of being smokers at 18 years of age however, no association was observed at 13-15 years (Huang et al, 2005). A second prospective study...

Mutagenesis versus selection

There is no basis to the view that TP53 lies in a hypermutable region of the genome. Thus, the high frequency and distribution of mutations reflects the acquisition of a selective advantage for tumorigenesis induced by the mutation. Indeed, inactivation of p53 function deletes a major cancer protection system by allowing cells with damaged DNA to replicate. Two main selection mechanisms can be proposed. The first accounts for the high rate of TP53 mutations in tumors arising from intense exposure to environmental carcinogens such as, for example, lung cancer in smokers. In normal lung cells of heavy smokers, the high load of DNA damage over long periods of time generates a global suppression of cell growth, only compensated by the capacity of the cells to keep p53 function under control. When tobacco carcinogens hit within the TP53 sequence to induce an inactivating mutation, the cell that has acquired such a mutation escapes stress-induced suppression and thus immediately gains a...

Pharmacodynamic Candidate Genes

The CHRNA5-CHRNA3-CHRNB4 locus and their haplotypes have been associated with the severity of nicotine dependence if daily smoking was initiated by or before 16 years of age (Weiss et al, 2008). This genetic association was lost among the smokers who started daily smoking after 16 years of age pointing toward a link between haplotypes on this locus and early nicotine exposure. Ehringer et al (2007) observed that a SNP located upstream of the CHRNB2 gene was associated with initial subjective response to tobacco, however, failed to observe any association of the CHRNA4 gene and nicotine dependence among young adults. The neurotransmitter, dopamine, is considered to be centrally involved in nicotine addiction. Thus, several studies have examined the associations of smoking with members of the dopaminer-gic pathway among adolescents. The ANKK1 gene, located upstream of the dopamine receptor 2 gene (DRD2), has a common variant referred to as TaqlA (rs1800497). This variant has been...

Perspectives p53 and cancer management

M., Jamshedur Rahman, S. M. et al. (2003). Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res, 63, 7113-21. Pfeifer, G. P., Denissenko, M. F., Olivier, M. et al. (2002). Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene, 21, 7435-51.

Summary of Pharmacogenetic Findings

Consistent associations with smoking cessation have been observed for genotypic and phenotypic measures of variation in nicotine metabolism (Lerman et al, 2006b Malaiyandi et al, 2006 Patterson et al, 2008 Schnoll et al, 2009). Findings for association of the COMT val158met polymorphism with response to nicotine patch therapy are also largely consistent, suggesting that smokers who carry the val allele have a greater risk for relapse (Colilla et al, 2005 Johnstone et al, 2007 Munafo et al, 2008). Findings for association of OPRM1 with smoking cessation warrant further attention. Although associations of the CHRNA5-A3-B4 gene cluster with nicotine dependence have been replicated in several studies (Bierut et al, 2008 Saccone et al, 2007 Thorgeirsson et al, 2008), evidence for association with smoking cessation is not consistent across studies (Baker et al, 2009 Breitling et al, 2008 Conti et al, 2008).

Colony Stimulating Factor Therapy

Abbreviations NHL, non-Hodgkin's lymphoma SCLC, small-cell lung cancer CAE, cyclophosphamide, doxorubicin, and etoposide VAPEC-B, vincristine, etoposide, cyclophosphamide, and bleomycin VNCOP-B, etoposide, procarbazine, cyclophosphamide, vincristine, and bleomycin rHuG-CSF, recombinant human granulocyte colony-stimulating factor. Abbreviations NHL, non-Hodgkin's lymphoma SCLC, small-cell lung cancer CAE, cyclophosphamide, doxorubicin, and etoposide VAPEC-B, vincristine, etoposide, cyclophosphamide, and bleomycin VNCOP-B, etoposide, procarbazine, cyclophosphamide, vincristine, and bleomycin rHuG-CSF, recombinant human granulocyte colony-stimulating factor.

With Mood Related Measures

There has been limited research investigating the effects of genetic variants on smoking-related changes in mood states. A recent study published by Perkins and colleagues (2008b) observed that cigarette liking was greater during negative vs. positive mood induction among participants that had the ANKK1 * T allele and the OPRM1 AA genotype. Latency to first puff was significantly shorter after negative vs. positive mood induction among smokers with the SLC6A3 9-repeat allele and the ANKK1 * T allele (Perkins et al, 2008b). Individuals with SLC6A3 9-repeat allele and the DRD2 C957T CC genotype also took a greater number of puffs during negative vs. positive mood induction (Perkins et al, 2008b).

With Smoking Phenotypes in Neuroimaging Studies

A recent PET study examined associations of dopaminergic gene variants with smoking-induced DA release using the radio-tracer 11C raclopride and observed that smokers carrying variants associated with reduced dopamin-ergic tone (i.e., SLC6A3 9-repeat allele, DRD4 S allele, or the COMT Val Val genotypes) had greater smoking-induced decreases in raclopride binding in the striatum, indicative of greater DA release in this region (Brody et al, 2006). A perfusion-MRI study after overnight abstinence found that genetic variants associated with reduced dopaminergic tone (DRD2-141 DelC variant and COMT Val Val genotype) and increased endogenous opioid binding (OPRM1 AA genotype) had greater regional abstinence-induced rCBF increases that may increase risk for relapse (Wang et al, 2008b). Jacobsen and colleagues (2006) investigated the association between the DRD2 C957T polymorphism and brain activation during a working memory task called the N-back task following pretreatment with either...

Future Directions

Genotype should be conducted in order to replicate the 'retrospective' findings obtained thus far in the context of treatment trials. Studies that investigate whether randomizing participants to different treatments based on nicotine metabolite ratio (as a pretreatment screening) increases smoking cessation rates would be a vital step toward extending the field from controlled clinical trials to clinical practice. Further, since varenicline is the most efficacious medication available, pharmacogenetic studies are needed to identify sub-groups of smokers who would benefit most from this treatment. Pharmacogenetic studies that focus on treatment efficacy should also focus on other longitudinal outcome measures such as lapses, relapses, and changes in smoking rate over time. Since treatment compliance is a significant issue in the context of treating nicotine dependence, pharmacoge-netic studies of nicotine dependence trials should focus on medication side effects or discontinuation of...

Use Of Csfs For Rbc Support 11 Introduction

Anemia is a common clinical problem in patients with lung cancer. Many patients with lung cancer exhibit anemia at diagnosis that may be aggravated by disease-specific therapy, which is often platinum-based. Many patients with lung cancer are symptomatic (1). In these patients, anemia may cause or aggravate shortness of breath and fatigue. Fatigue is the most often reported symptom in cancer patients receiving chemotherapy and has profound consequences on quality of life (QOL) (2). Anemia can be responsible for delay or reduction of cytotoxic treatment, and it is an independent negative prognostic factor of disease outcome (3,4). The impact of anemia in patients with lung cancer is largely underestimated by the medical community. Despite substantial evidence that treatment of anemia reduces the number of transfusions (and the associated risks) and improves QOL, many clinicians still only treat with red blood cell (RBC) transfusions if their patients' hemoglobin (Hb) concentration...

Causes of Anemia in Patients

Anemia in patients with lung cancer has a multifactorial etiology (6). Contributing factors are the anemia of chronic disorders, concomitant postobstructive respiratory infections, tumor-induced autoimmune hemolysis, and bone marrow invasion or dysfunction caused by the tumor. These patients can also have iron, folate, or vitamin B12 deficiency, as well as blood loss from tumor erosion. Endogenous EPO is of particular interest, since anemic cancer patients have been shown to have inappropriately low amounts of circulating EPO for their degree of anemia, reflecting a perturbation in this homeostatic mechanism, with loss of the normally expected inverse linear relation between serum EPO and Hb concentrations (7,8). In a study with a very homogenous group of chemotherapy- and radiotherapy-naive patients with lung cancer, analysis of serum EPO and soluble transferrin receptor suggested that impaired erythroid marrow response to EPO and a relative inadequacy of EPO production were...

Incidence of Anemia in Patients

The prevalence of pretreatment anemia varies across different solid tumor types. In an anemia audit, up to 60 of patients with lung cancer had Hb values < 11 g dL, a considerably higher prevalence than in patients with colorectal or breast cancer (10-20 ). Consequently, approx 40 of patients with lung cancer needed blood transfusions, compared with only about 20 of patients with breast cancer (16). The proportion of patients with anemia increases over the course of treatment. The problem of anemia in patients undergoing chemotherapy has been reviewed for NSCLC (17) and for cancer in general (18). A larger variation in both mild-to-moderate anemia (Hb concentration > 8.0 g dL) in 8-100 of patients with lung cancer and severe anemia (Hb concentration < 8.0 g dL) in 0-55 was reported. In a retrospective analysis including 128 patients with lung cancer, chemotherapy significantly decreased Hb concentrations compared with pretreatment values, with a significantly more prominent...

Percutaneous Administration

Organic phosphates diisopropyl fluorophosphate (DFP), parathion, and malathion and nicotine insecticides have caused deaths in agricultural workers as a result of percutaneous absorption upon in-field contact. Chlorovinyl arsine dichloride (lewisite), a mustard gas, is readily absorbed through the skin and has been used in chemical warfare. Most of the carcinogens in the atmosphere can be efficiently absorbed through the skin and it is no wonder that there is a higher cancer incidence rate in people living around the industrial centers, even though these people may not be directly exposed to these chemicals.

Effect of Anemia on Disease Outcome

A Hb concentration > 11.0 g dL was a significantly (p 0.001) favorable prognostic factor in a large retrospective analysis of 2531 patients with advanced NSCLC (67). The relationship between anemia and survival was examined in a review of 60 papers, 25 of which were about lung cancer (3). The relative risk of death of anemic patients with lung cancer increases by 19 (95 confidence interval (CI) 10-29). This effect is present regardless of whether the patients are treated with chemotherapy, radiotherapy, or surgery (4). An important additional question is whether this effect is because the lower Hb values are a sign of more advanced disease, or whether the anemia compromises anticancer treatment and thereby survival. In the last scenario, treatment of anemia might improve disease control and outcome. Several theoretical arguments (the role of tumor hypoxia in resistance to therapy 68 ) and patient data, in the fields of both radiotherapy (especially for head-and-neck and gynecologic...

Prenatal Antecedents of Allergies and Asthma

As can be seen in Fig. 35.2, clinical allergists now believe that the initial biases toward atopic disorders and asthma begin before birth (Jones et al, 2000). Maternal exposure to allergens, tobacco smoke, and pollution increases the risk that infants will wheeze during the first year of life and subsequently develop asthma by 3-4 years of age. Early warning signs of being prone to atopy can often be detected in cord blood. Two neonatal indicators are (1) the presence of elevated levels of IgE, the antibody class associated

Recommendations for the Use of Erythropoietic Factors

Anemia is a problem in up to 50-60 of patients with lung cancer, especially if they are treated with platinum-based chemotherapy. Despite its well-documented profound impact on QOL, many clinicians only treat with transfusion, once severe anemia (Hb concentration < 8 g dL) is present. Much evidence supports the use of rHuEPO for chemotherapy-induced anemia, if the Hb concentration decreases by < 10 g dL (79). Although recent data suggest that QOL may be preserved better if rHuEPO is started when the Hb concentration is < 12 g dL, there is at present not enough evidence to make an overall recommendation for this strategy, but rather clinical evidence in particular circumstances. include reduced time missed from work for physician visits and potentially better patient compliance. In a large randomized, placebo-controlled, phase 3 study in patients with lung cancer, using an administrations schedule of 2.25 pg kg once weekly, darbepoetin alfa showed a statistically significant and...

Use Of Csfs For Wbc Support

Neutropenia is a common side effect of chemotherapy for lung cancer. Neutropenia can be associated with febrile neutropenia (FN), neutropenic sepsis, which may be life-threatening, prolonged hospital admission for administration of iv antibiotics, and increased cost. Grade and duration of neutropenia have been correlated with the risk of developing sepsis. This section reviews the use of rHuG-CSF or rHuGM-CSF in lung cancer in these different settings, based on published randomized data. Finally, some guidelines for the use of white blood cell (WBC)-stimulating cytokines in the clinical approach to patients with lung cancer are given.

Recommendations for the Use of White Blood Cell CSFs 231 Primary Administration

Ommend reserving primary administration of CSF for patients with an expected incidence rate of FN of at least 40 (112). Thus, for most standard chemotherapy regimens for patients with lung cancer, primary administration of CSF is not recommended. Guidelines, however, recognize that there are some clinical situations in which the use of CSF might be appropriate, as in the case of patients at high risk for postobstructive pneumonia, with extensive prior chemotherapy and or irradiation, with a history of recurrent FN while receiving earlier chemotherapy, or with decreased immune function. The recommended dose is 5 g kg per day for rHuG-CSF (filgrastim) and 250 g m2 per day for rHuGM-CSF (sargramostim), to be started between 24 and 72 h after chemotherapy until the occurrence of a neutrophil count of 10 x 109 L. CSFs should be avoided in patients receiving concomitant chemoradiation. Although some limited evidence exists that CSFs can decrease the probability of FN in subsequent cycles of...

Environmental factors

Failed to identify the major causative factor(s). Many environmental factors have been proposed as causative agents for IBD (Table 20.1). From these, diet, domestic hygiene and micro-organisms were the most investigated areas (Andersson et al., 2001 Bull et al., 2003 Cosnes et al., 1999 Darfeuille-Michaud et al., 1998 Ekbom et al., 1990 Ekbom et al., 1996 Gent et al., 1994 Gilat et al., 1987 Godet et al., 1995 Greenstein, 2003 Kallinowski et al., 1998 Lamps et al., 2003 Persson etal., 1987 Sanderson etal., 1992 Thompson etal., 1995). In fact the only risk factors that can be currently supported are appendectomy, which has a protective role in UC, and tobacco. Smoking protects against UC (OR 0.41 (0.34-0.48) and improves the disease course (Calkins, 1989). On the other hand, smoking increases the risk of CD (OR 2.0 (1.65-2.47)) and the severity of the disease, as shown by an increased use of immu-nosuppressant agents and surgical intervention in smokers (Calkins, 1989 Cosnes et al.,...

Individual Level Child Health Behaviors

That adolescent cigarette smoking increases as parent income and education decrease and that this relationship may be partially mediated by parental smoking habits. These results are supported by a national longitudinal study which also found inverse SES gradients for cigarette smoking and alcohol use (Goodman and Huang, 2002). However, this study also reported that the nature of the relationships was not consistent across all SES indicators. Longitudinally, Harrell et al (1998) found that low SES children and adolescents were more likely to be experimental smokers and to start smoking earlier. In contrast, some evidence suggests that substance use may be more common among adolescents from high SES families (Hanson and Chen, 2007), perhaps because it is easier for high SES youth to acquire cigarettes, alcohol, and other drugs due to greater financial resources or because youth from affluent backgrounds are not exposed to the negative consequences of drug use on a regular basis which...

Basic Fibroblast Growth Factor

Basic fibroblast growth factor (bFGF) was one of the first angiogenic factors to be characterized and since then has been studied extensively. It induces tube formation in collagen gels, modulates integrin expression and gap junction intercellular communication, and it upregulates VEGF, VEGFR2, and uPAR in vitro (44). bFGF stimulates both lymphangiogenesis and angiogenesis in a mouse corneal lymphangiogenesis model and up-regulats VEGF-C expression in vascular endothelial and perivascular cells (45). It is one of the most potent angiogenic factors and high serum levels upon diagnosis are associated with poor outcomes for cases of lung cancer (46).

Estrogen Deprivation Increases Risk for Depression and Medical Illness

American Menopause Society, 2006), it is of interest here that the WHI was also the first large-scale controlled trial to demonstrate a significant reduction in hip fracture of about 35 associated with ERT and HRT use (Anderson et al, 2004 Cauley et al, 2003). While the controversy currently surrounding the use of ERT or HRT in postmenopausal women has limited its use in the prevention of osteoporosis, that estrogen can prevent bone loss in postmenopausal women at doses lower than those required to stimulate classic target tissues such as breast and uterus (Prestwood et al, 2003), suggests a more favorable cost benefit ratio for estrogen in the treatment of osteoporosis. Controlled trials will be needed in order to confirm this. It should also be noted that there are a number of other available FDA approved pharmacotherapy options that have also proven to be efficacious in the treatment of osteoporosis, these include bispho-sphonates, calcitonin, and parathyroid hormone medications...

Paracrine Regulation of Blood Flow

Cocaine inhibits the reuptake of norepinephrine into the adrenergic axons, resulting in enhanced sympathetic-induced vasoconstriction. Chest pain, as a result of myocardial ischemia produced in this way, is a common cocaine-related problem. The nicotine from cigarette smoke acts synergistically with cocaine to induce vasoconstriction.

Lifestyle Behaviors in Old

Aging has generally rather profound effects on lifestyle behaviors as well, either due to changes in daytime activities (e.g., after retirement or widowhood) or as a result of the considerable increase in disabilities and chronic diseases associated with aging. Specifically, the degree of physical activity may decrease due to physical decline, acquired chronic conditions, and accompanying pain. But other lifestyle behaviors might also be affected. Smoking is an important accelerator of the aging process. In general, the percentage of persons smoking decreases with increasing age, but this may in large part be due to the selective survival of non-smokers, or due to the fact that certain older persons stop smoking because of health reasons. It is important to note, however, that those persons who smoke most probably have been smoking a large part of their lives. This accumulating effect of lifetime smoking might therefore be specifically detrimental in older persons. As with smoking,...

Clinical Manifestations

Another manifestation of LCH is primary pulmonary LCH, which affects both children and adults. Pulmonary LCH has been associated with cigarette smoking in adults, and the course tends to be severe. The childhood form of pulmonary LCH appears to be less severe but more chronic in nature (6).

Granulocyte Colonystimulating Factor And Granulocytemacrophage Colonystimulating Factor For Chemotherapyinduced

Crawford et al. (19) did a randomized, double-blind, placebo-controlled trial in patients with small-cell lung cancer (SCLC) to evaluate the incidence of fever and neutropenia in patients treated with chemotherapy. Two-hundred eleven patients receiving chemotherapy with cyclophosphamide, doxorubicin, and etoposide (CAE)

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